Variant in CACNA1G as a Possible Genetic Modifier of Neonatal Epilepsy in an Infant with a De Novo SCN2A Mutation.

Mutations in SCN2A genes have been described in patients with epilepsy, finding a large phenotypic variability, from benign familial epilepsy to epileptic encephalopathy. To explain this variability, it was proposed the existence of dominant modifier alleles at one or more loci that contribute to determine the severity of the epilepsy phenotype. One example of modifier factor may be the CACNA1G gene, as proved in animal models. We present a 6-day-old male newborn with recurrent seizures in which a mutation in the SCN2A gene is observed, in addition to a variant in CACNA1G gene. Our patient suffered in the first days of life myoclonic seizures, with pathologic intercritical electroencephalogram pattern, requiring multiple drugs to achieve adequate control of them. During the next weeks, the patient progressively improved until complete remission at the second month of life, being possible to withdraw the antiepileptic treatment. We propose that the variant in CACNA1G gene could have acted as a modifier of the epilepsy syndrome produced by the mutation in SCN2A gene in our patient.

Prevalencia de dolor y su abordaje terapéutico en niños pasibles de cuidados paliativos asistidos en un centro de referencia de Uruguay / Prevalence of pain and its therapeutic approach in children eligible for assisted palliative care in a reference hospital center in Uruguay / Prevalência de dor e sua abordagem terapêutica em crianças submetidas a cuidados paliativos atendidas em um centro hospitalar de referência no Uruguai

Introducción: el tratamiento del dolor es un derecho humano y constituye un pilar de los cuidados paliativos (CP). Este síntoma en niños suele ser subestimado e insuficientemente tratado. Objetivo: conocer la prevalencia del dolor y describir el perfil de uso de fármacos analgésicos, coadyuvantes y procedimientos invasivos en niños asistidos en la Unidad de Cuidados Paliativos Pediátricos del Centro Hospitalario Pereira Rossell (UCPP-CHPR) durante el período 2019-2021. Metodología: se realizó un estudio observacional, descriptivo y retrospectivo mediante revisión de historias clínicas. Resultados: se incluyeron 317 niños, 58% de sexo masculino, con una mediana de edad 6,9 años. Eran portadores de enfermedades neurológicas severas no evolutivas 64%, utilizaban prótesis o tecnología médica 51%. Se encontró registro de presencia de dolor en 35%, de tipo crónico 87%, mixto 55% y de fuentes múltiples 54%. Se detectó uso de escala para evaluación del dolor en 61%, la más utilizada fue r-FLACC. En el grupo de niños con dolor se encontró prescripción de analgésicos en 43% (48/111) y de coadyuvantes 87% (97/111), gabapentina en 78. En todos la vía de administración fue la oral/enteral. Se encontró uso off label de fármacos en 79% y polifarmacia en 82%. Se registraron efectos adversos en 10%. Conclusión: un tercio de los niños asistidos por la UCPP-CHPR, presentaba registros de presencia dolor. La mayoría de tipo crónico, mixto y de fuentes múltiples. Se encontró amplio uso de escalas validadas para evaluación del dolor y alta prescripción de coadyuvantes en relación a la de analgésicos.

Introduction: pain treatment is a human right and a pillar of palliative care (PC). This symptom in children is often underestimated and insufficiently treated. Objective: learn about the prevalence of pain and describe the analgesic drugs' usage profile, adjuvants and invasive procedures in children assisted in the Pediatric Palliative Care Unit of the Pereira Rossell Hospital Center (UCPP-CHPR) during the period 2019-2021. Methodology: observational, descriptive and retrospective study based on the review of medical records. Results: 317 children were included, 58% male, with a median age of 6.9 years. 64% were carriers of severe non-progressive neurological diseases, 51% used prosthetics or medical technology. A record of the presence of pain was found in 35%, chronic type 87%, mixed 55% and multiple sources 54%. The use of a pain assessment scale was detected in 61%, the most used was r-FLACC. In the group of children with pain, analgesics were prescribed in 43% (48/111) and adjuvants in 87% (97/111), gabapentin in 78. In all of them, the administration route was oral/enteral. Off-label use of drugs was found in 79% and polypharmacy in 82%. Adverse effects were recorded in 10%. Conclusion: a third of the children assisted by the UCPP-CHPR showed records of pain presence. Most chronic type, mixed and multiple sources. We found a vast use of validated scales for pain assessment and high prescription of adjuvants in relation to analgesics.

Introdução: o tratamento da dor é um direito humano e constitui um pilar dos Cuidados Paliativos (CP). Este sintoma em crianças é geralmente subestimado e insuficientemente tratado. Objetivo: conhecer a prevalência da dor e descrever o perfil do uso de medicamentos analgésicos, adjuvantes e procedimentos invasivos em crianças atendidas na Unidade de Cuidados Paliativos Pediátricos do Centro Hospitalar Pereira Rossell (UCPP-CHPR) durante o período de 2019-2021. Metodologia: foi realizado um estudo observacional, descritivo e retrospectivo por meio de revisão de prontuários. Resultados: foram incluídas 317 crianças, 58% do sexo masculino, com idade mediana de 6,9 anos. 64% eram portadores de doenças neurológicas graves não evolutivas, 51% usavam próteses ou tecnologia médica. Registro da presença de dor foi encontrado em 35%, do tipo crônica 87%, mista 55% e de origem múltipla 54%. A utilização de escala para avaliação da dor foi detectada em 61%, sendo a mais utilizada a r-FLACC. No grupo de crianças com dor, a prescrição de analgésicos foi encontrada em 43% (48/111) e adjuvantes em 87% (97/111), gabapentina em 78. Ao todo, a via de administração foi oral/enteral. Uso off-label de medicamentos foi encontrado em 79% e polifarmácia em 82%. Efeitos adversos foram registrados em 10%. Conclusão: um terço das crianças atendidas pela UCPP-CHPR apresentou registro da presença de dor. A maioria do tipo crônica, mista e de fontes múltiplas. Encontrou-se ampla utilização de escalas validadas para avaliação da dor e elevada prescrição de coadjuvantes em relação aos analgésicos.

Exploring the role of ecology and social organisation in agropastoral societies: A Bayesian network approach.

The present contribution focuses on investigating the interaction of people and environment in small-scale farming societies. Our study is centred on the particular way settlement location constraints economic strategy when technology is limited, and social division of work is not fully developed. Our intention is to investigate prehistoric socioeconomic organisation when farming began in the Old World along the Levant shores of Iberian Peninsula, the Neolithic phenomenon. We approach this subject extracting relevant information from a big set of ethnographic and ethnoarchaeological cases using Machine Learning methods. This paper explores the use of Bayesian networks as explanatory models of the independent variables-the environment- and dependent variables-social decisions-, and also as predictive models. The study highlights how subsistence strategies are modified by ecological and topographical variables of the settlement location and their relationship with social organisation. It also establishes the role of Bayesian networks as a suitable supervised Machine Learning methodology for investigating socio-ecological systems, introducing their use to build useful data-driven models to address relevant archaeological and anthropological questions.

Extending the clinical phenotype of SPTAN1: From DEE5 to migraine, epilepsy, and subependymal heterotopias without intellectual disability.

Mutations in SPTAN1 gene, encoding the nonerythrocyte αII-spectrin, are responsible for a severe developmental and epileptic encephalopathy (DEE5) and a wide spectrum of neurodevelopmental disorders, as epilepsy with or without intellectual disability (ID) or ID with cerebellar syndrome. A certain genotype-phenotype correlation has been proposed according to the type and location of the mutation. Herein, we report three novel cases with de novo SPTAN1 mutations, one of them associated to a mild phenotype not previously described. They range from (1) severe developmental encephalopathy with ataxia and a mild cerebellar atrophy, without epilepsy; (2) moderate intellectual disability, severe language delay, ataxia and tremor; (3) normal intelligence, chronic migraine, and generalized tonic-clonic seizures. Remarkably, all these patients showed brain MRI abnormalities, being of special interest the subependymal heterotopias detected in the latter patient. Thus we extend the SPTAN1-related phenotypic spectrum, both in its radiological and clinical involvement. Furthermore, after systematic analysis of all the patients so far reported, we noted an excess of male versus female patients (20:9, p = 0.04), more pronounced among the milder phenotypes. Consequently, some protection factor might be suspected among female carriers, which if confirmed should be considered when establishing the pathogenicity of milder genetic variants in this gene.

Luxury zinc supply acts as antiaging agent and enhances reproductive fitness in Arabidopsis thaliana.

Developmental senescence in plants is an age dependent process affected by phytohormones, nutrient status, and environmental factors, while the antiaging effects of zinc are recognized in humans. This study explores the possible influence of a high, non-toxic Zn-supply (12 µM) on senescence and reproductive fitness in A. thaliana. Auxin-resistance mutant, axr1-12, and auxin overexpressing YUCCA6 mutant, yuc6-1D, and their corresponding background genotypes were grown until complete rosette senescence to quantify the fruit biomass and seed number. Gene expression of different antioxidant, auxin and senescence-associated markers were analyzed after the onset of senescence. All mutants showed delayed developmental senescence. Luxury Zn delayed senescence in wild type, but not in the mutant genotypes. Excluding axr1-12 mutants, which showed very low expression of the auxin gene marker INDOLE-3-ACETIC ACID INDUCIBLE 2 (IAA2), enhanced expression of the senescence markers SENESCENCE-ASSOCIATED GENE 12 (SAG12) and AUXIN RESPONSE FACTOR 2 (ARF2) coincided with decreased expression of IAA2. Delayed senescence and total number of seeds per plant were related to higher expression of the peroxisomal antioxidant enzymes Cu/Zn superoxide dismutase (SOD3) and catalase (CAT2). These results evidence that high Zn-induced delayed senescence and improved reproductive fitness in Arabidopsis are related to an auxin-independent mechanism that retains antioxidant activity.

Health care contact prior to suicide attempts in older adults. A field study in Galicia, Spain.

INTRODUCTION: Older people have the highest suicide rates in the world. In turn, they have the lowest rates of suicide attempts. Many studies have found greater health contact, especially with general practitioner, prior to suicidal behaviour in this age group. Less information is availbale about prior contact with other health services. OBJECTIVE: The objective of the study is to know the characteristics of contact with all levels of health services, prior to a suicide attempt in people over 65 years of age in a defined population. MATERIAL AND METHODS: Along the period January 2015 to December 2017, all persons over 65 years of age admitted by suicide attempt to emergency room in the health area of Santiago de Compostela were interviewed. The interview included a psychiatric evaluation and the collrection of relevant clinical and sociodemographic variables, in particular, data on prior contact with health services. RESULTS: 80 suicide attempts were recorded, which represents an incidence of 35.3 / 100,000. The average age of our sample was 74.85 ± 7 years, the ratio between male: female was 2: 3. 61.3% had visited their general practitioner the month prior to the attempt, 72.5% had visited a health centre. On the other hand, 41.3% were not under the follow up of Mental Health services. CONCLUSIONS: The facts hat two out of three people over 65 years who commit suicide attempt in our area visit their general practitioner the previous month and 90% visit a health service along the previous three months, raise the question of wheter preventive measures of suicide could take place beyond the scope of Primary Care.

Percutaneous closure of an atrial septal defect in a patient with Ebstein anomaly and right-to-left shunt.

Ebstein anomaly is a congenital disease frequently associated with atrial septal defects, which can generate a right-to-left shunt, leading to systemic desaturation and right ventricular failure. We describe the case of a 68-year-old man with central cyanosis due to Ebstein anomaly and a patent foramen ovale. An atrial septal occluder was initially implanted after having performed prolonged test occlusion of the interatrial communication. In this case, device embolization occurred due to high right pressure. Percutaneous closure of atrial septal defects in the presence of a right-to-left shunt can offer a significant clinical improvement in selected cases. In patients with Ebstein anomaly, the implantation of atrial septal defect closure devices may be desirable, due to the larger size of the waist, which may provide better stability in the event of an increase in right pressure.

Contrasting allocation of magnesium, calcium and manganese in leaves of tea (Camellia sinensis (L.) Kuntze) plants may explain their different extraction efficiency into tea.

During tea preparation mineral elements are extracted from the dried leaves of tea (Camellia sinensis (L.) Kuntze) plants into the solution. Micro-particle induced X-ray emission was employed to investigate the spatial distribution of magnesium (Mg), calcium (Ca) and manganese (Mn) in the young and old leaves of tea plants grown in the absence and presence of aluminium (Al) in the substrate. Results revealed that in tea leaves the largest concentrations of Mg occurred in the epidermis, of Ca in oxalate crystals and of Mn in epidermis and oxalate crystals; there was a leaf-age effect on tissue-specific concentrations of Mg, Ca and Mn with all tissues of old leaves containing larger concentrations of Mg, Ca and Mn than young leaves; supplementation of substrate with Al reduced concentrations of Mg, Ca and Mn in the old leaves, and a link between the distribution of Mg, Ca and Mn in the tea leaves with the extraction efficiencies of these elements into the tea was possible. We conclude that old leaves of tea plants cultivated under conditions of low Al availability will have the largest concentrations of Mg, Ca and Mn and may represent most acceptable ingredient for the preparation of tea.

How Plants Handle Trivalent (+3) Elements.

Plant development and fitness largely depend on the adequate availability of mineral elements in the soil. Most essential nutrients are available and can be membrane transported either as mono or divalent cations or as mono- or divalent anions. Trivalent cations are highly toxic to membranes, and plants have evolved different mechanisms to handle +3 elements in a safe way. The essential functional role of a few metal ions, with the possibility to gain a trivalent state, mainly resides in the ion's redox activity; examples are iron (Fe) and manganese. Among the required nutrients, the only element with +3 as a unique oxidation state is the non-metal, boron. However, plants also can take up non-essential trivalent elements that occur in biologically relevant concentrations in soils. Examples are, among others, aluminum (Al), chromium (Cr), arsenic (As), and antimony (Sb). Plants have evolved different mechanisms to take up and tolerate these potentially toxic elements. This review considers recent studies describing the transporters, and specific and unspecific channels in different cell compartments and tissues, thereby providing a global vision of trivalent element homeostasis in plants.

Snails prefer it sweet: A multifactorial test of the metal defence hypothesis.

Metal defence against insect herbivory in hyperaccumulator plants is well documented. However, there are contradictory results regarding protection against snails. According to the joint effects hypothesis, inorganic and organic defences cooperate in plant protection. To test this hypothesis, we explored the relationships between snail (Cantareus aspersus) feeding and multiple inorganic and organic leaf components in the Cd hyperaccumulator plant Noccaea praecox. Plants grouped by rosette size growing in nutrient solution supplemented or not with 50 µM Cd were offered to the snails. After 3 days of snail feeding, the plants and snails were analysed. In addition to Cd concentrations, we analysed leaves for nutritional factors (sugar and protein), defence-related compounds (glucosinolates, phenolics, tannins, salicylic acid and jasmonate) and essential mineral nutrients. Cadmium concentrations in the snails and in snail excrements were also analysed. Snails preferentially fed on plants grown without Cd. Medium-sized plants exposed to Cd were the least consumed. Snail excrements from this trial weighed less and had higher Cd concentrations than those from other treatments. Cadmium increased salicylate and jasmonate production. A positive relationship between jasmonate levels and the number of attacked leaves was found. Principal component analysis revealed that leaf sugar concentration was the main factor positively affecting snails' leaf consumption, while leaf Cd had a negative but weaker influence. In conclusion, leaf sugar concentration mainly governs snails' feeding preferences. High leaf Cd concentrations do not deter herbivores from attacking leaves, but they do reduce leaf consumption. Our results clearly support the joint effects hypothesis.

Highly diverse Bronze Age population dynamics in Central-Southern Europe and their response to regional climatic patterns.

The reconstruction of past demographic patterns is a fundamental step towards a better understanding of human-environment relations, especially in terms of quantifiable anthropic impact and population susceptibility to environmental changes. The recently developed Summed Calibrated Probability Distributions (SCPD) approach, based on large collections of archaeological radiocarbon dates, provides a new tool to obtain continuous prehistoric population curves suitable for comparison with palaeoenvironmental time series. Despite a wide application in Mesolithic and Neolithic contexts worldwide, the use of the SCPD method remains rare for post-Neolithic societies. Our aim is to address this visible gap and apply the SCPD approach to South European archeological contexts between the Bronze Age and the transition into the Iron Age (1800-800 cal. BC), then evaluating these results against local archeological narratives and palaeoecological data. We first test the SCPD method at a supra regional scale, ranging from the Ebro to the Danube rivers, and subsequently in five selected regions within this area. We then compare the regional population curves to climate data reconstructed from local palynological records. Our results highlight the contrast between a stable supra regional demographic trend and more dynamic regional patterns. We do not observe any convincing long-term correlations between population and climate, but localized episodes of demographic stagnation or decline are present in conjunction with climatic shifts or extremes. Nevertheless, climate change as a triggering factor should be considered with caution, especially in peripheral areas where the archaeological data is faint, or where local evidence points to contemporaneous, ongoing landscape overexploitation.

Transport and Use of Bicarbonate in Plants: Current Knowledge and Challenges Ahead.

Bicarbonate plays a fundamental role in the cell pH status in all organisms. In autotrophs, HCO3− may further contribute to carbon concentration mechanisms (CCM). This is especially relevant in the CO2-poor habitats of cyanobacteria, aquatic microalgae, and macrophytes. Photosynthesis of terrestrial plants can also benefit from CCM as evidenced by the evolution of C4 and Crassulacean Acid Metabolism (CAM). The presence of HCO3− in all organisms leads to more questions regarding the mechanisms of uptake and membrane transport in these different biological systems. This review aims to provide an overview of the transport and metabolic processes related to HCO3− in microalgae, macroalgae, seagrasses, and terrestrial plants. HCO3− transport in cyanobacteria and human cells is much better documented and is included for comparison. We further comment on the metabolic roles of HCO3− in plants by focusing on the diversity and functions of carbonic anhydrases and PEP carboxylases as well as on the signaling role of CO2/HCO3− in stomatal guard cells. Plant responses to excess soil HCO3− is briefly addressed. In conclusion, there are still considerable gaps in our knowledge of HCO3− uptake and transport in plants that hamper the development of breeding strategies for both more efficient CCM and better HCO3− tolerance in crop plants.

A proteomic approach to the mechanisms underlying activation of aluminium resistance in roots of Urochloa decumbens.

The mechanisms of extreme Al-resistance in Urochloa decumbens are not established. Full resistance expression requires a lag time of 72-96h and is preceded by a sensitive phase (24-48h) with Al-induced root growth inhibition. The aim here was to identify key processes of the activation phase of Al-resistance analysing both root exudates and comparative root proteome. Samples were taken after 0, 24 and 96h exposure to 0 or 200µM Al. Al-induced stimulation of citrate and oxalate efflux was limited to the sensitive phase. Only 11 proteins revealed Al-induced abundance differences; six were identified. After 24h, phenylalanine ammonium lyase (PAL), methionine synthase (MS), and deoxymugineic acid synthase (DMAS) decreased, while acid phosphatase (APase) abundance increased. Coincident with growth recovering, PAL and MS, but not DMAS, returned to initial levels. After 96h, γ­carbonic anhydrase (γ­CA) and adenylate kinase (AK) along with two unidentified proteins were more abundant. In conclusion, few protein changes characterize the initial response to Al in signalgrass. During the alarm phase, changes are related to P-mobilization, downregulation of Fe-acquisition, reduction of phenolic biosynthesis, and small stimulation of organic acid exudation. After recovering (resistant phase), biosynthesis of phenolics and methionine, but not Fe-mobilization are re-established. Full expression of Al-resistance is characterized by enhanced γ­CA mediating mitochondrial complex I assembly and increased AK abundance indicating higher root respiration and better provision of ADP and Mg2+ to ATP synthase, respectively. The unidentified proteins and the specific role of γ­CA in Al resistance of U. decumbens will centre future research.

Zinc hyperaccumulation substitutes for defense failures beyond salicylate and jasmonate signaling pathways of Alternaria brassicicola attack in Noccaea caerulescens.

The hypothesis of metal defense as a substitute for a defective biotic stress signaling system in metal hyperaccumulators was tested using the pathosystem Alternaria brassicicola-Noccaea caerulescens under low (2 µM), medium (12 µM) and high (102 µM) Zn supply. Regardless the Zn supply, N. caerulescens responded to fungal attack with the activation of both HMA4 coding for a Zn transporter, and biotic stress signaling pathways. Salicylate, jasmonate, abscisic acid and indoleacetic acid concentrations, as well as biotic stress marker genes (PDF1.2, CHIB, LOX2, PR1 and BGL2) were activated 24 h upon inoculation. Based on the activation of defense genes 24 h after the inoculation an incompatible fungal-plant interaction could be predicted. Nonetheless, in the longer term (7 days) no effective protection against A. brassicicola was achieved in plants exposed to low and medium Zn supply. After 1 week the biotic stress markers were even further increased in these plants, and this compatible interaction was apparently not caused by a failure in the signaling of the fungal attack, but due to the lack of specificity in the type of the activated defense mechanisms. Only plants receiving high Zn exhibited an incompatible fungal interaction. High Zn accumulation in these plants, possibly in cooperation with high glucosinolate concentrations, substituted for the ineffective defense system and the interaction turned into incompatible. In a threshold-type response, these joint effects efficiently hampered fungal spread and, consequently decreased the biotic stress signaling.

Zinc triggers signaling mechanisms and defense responses promoting resistance to Alternaria brassicicola in Arabidopsis thaliana.

According to the elemental defense hypothesis the accumulation of trace elements by plants may substitute for organic defenses, while the joint effects hypothesis proposes that trace elements and organic defenses can have additive or synergistic effects against pathogens or herbivores. To evaluate these hypotheses the response of the pathosystem Alternaria brassicicola-Arabidopsis thaliana to control (2µM) and surplus (12µM) Zn was evaluated using the camalexin deficient mutant pad3-1 and mtp1-1, a mutant with impaired Zn vacuolar storage, along with the corresponding wildtypes. In vitro, a 50% inhibition of fungal growth was achieved by 440µM Zn. A. thaliana leaves could accumulate equivalent concentrations without harm. In fact, surplus Zn enhanced the resistance of A. thaliana to fungal attack in Columbia (Col-0), Wassilewskija (WS), and mtp1-1. However, surplus Zn was unable to protect pad3-1 demonstrating that Zn cannot substitute for camalexin, the main organic defense in A. thaliana. High, non phytotoxic leaf Zn concentrations enhanced the resistance to A. brassicicola of A. thaliana genotypes able to produce camalexin. This was mainly due to Zn-induced enhancement of the JA/ETH signaling pathway leading to enhanced PAD3 expression. These results support the joint effects hypothesis and highlight the importance of adequate Zn supply for reinforced pathogen resistance.

A highly versatile and easily configurable system for plant electrophysiology.

In this study we present a highly versatile and easily configurable system for measuring plant electrophysiological parameters and ionic flow rates, connected to a computer-controlled highly accurate positioning device. The modular software used allows easy customizable configurations for the measurement of electrophysiological parameters. Both the operational tests and the experiments already performed have been fully successful and rendered a low noise and highly stable signal. Assembly, programming and configuration examples are discussed. The system is a powerful technique that not only gives precise measuring of plant electrophysiological status, but also allows easy development of ad hoc configurations that are not constrained to plant studies. •We developed a highly modular system for electrophysiology measurements that can be used either in organs or cells and performs either steady or dynamic intra- and extracellular measurements that takes advantage of the easiness of visual object-oriented programming.•High precision accuracy in data acquisition under electrical noisy environments that allows it to run even in a laboratory close to electrical equipment that produce electrical noise.•The system makes an improvement of the currently used systems for monitoring and controlling high precision measurements and micromanipulation systems providing an open and customizable environment for multiple experimental needs.

Differential activation of genes related to aluminium tolerance in two contrasting rice cultivars.

Rice (Oryza sativa) is a highly Al-tolerant crop. Among other mechanisms, a higher expression of STAR1/STAR2 (sensitive to Al rhizotoxicity1/2) genes and of Nrat1 (NRAMP Aluminium Transporter 1), and ALS1 (Aluminium sensitive 1) can at least in part be responsible for the inducible Al tolerance in this species. Here we analysed the responses to Al in two contrasting rice varieties. All analysed toxicity/tolerance markers (root elongation, Evans blue, morin and haematoxylin staining) indicated higher Al-tolerance in variety Nipponbare, than in variety Modan. Nipponbare accumulated much less Al in the roots than Modan. Aluminium supply caused stronger expression of STAR1 in Nipponbare than in Modan. A distinctively higher increase of Al-induced abscisic acid (ABA) accumulation was found in the roots of Nipponbare than in Modan. Highest ABA levels were observed in Nipponbare after 48 h exposure to Al. This ABA peak was coincident in time with the highest expression level of STAR1. It is proposed that ABA may be required for cell wall remodulation facilitated by the enhanced UDP-glucose transport to the walls through STAR1/STAR2. Contrastingly, in the roots of Modan the expression of both Nrat1 coding for a plasma membrane Al-transporter and of ALS1 coding for a tonoplast-localized Al transporter was considerably enhanced. Moreover, Modan had a higher Al-induced expression of ASR1 a gene that has been proposed to code for a reactive oxygen scavenging protein. In conclusion, the Al-exclusion strategy of Nipponbare, at least in part mediated by STAR1 and probably regulated by ABA, provided better protection against Al toxicity than the accumulation and internal detoxification strategy of Modan mediated by Nrat1, ALS1 and ARS1.

A case with reversible neurotoxicity after 2 years of dementia secondary to maintenance lithium treatment.

Chronic neurotoxicity caused by lithium salts can be reversible or irreversible and may appear after years of treatment, even at serum levels considered within the usual therapeutic range. The authors present the case of a patient with bipolar disorder who developed dementia at the age of 54 after being treated with lithium carbonate at therapeutic levels for 4 years. Nevertheless, lithium treatment was continued. At age 56, the patient presented with an acute encephalopathy caused by toxic lithium levels, which resolved only after lithium carbonate was discontinued. Full recovery from the dementia, which had started 2 years earlier, occurred only after cessation of lithium. The authors conclude that when patients treated with lithium develop subacute cognitive impairment, the possibility of lithium toxicity should be considered, even if the serum levels are considered within the therapeutic range. A long duration of neurotoxicity associated with lithium treatment does not necessarily indicate an irreversible prognosis.